The proposed research project will investigate means for inducing immunity to lower respiratory tract disease caused by nontypable Hemophilus influenza (NTHI). This bacterial organism is an important cause of both tracheobronchitis and pneumonia in elderly or debilitated persons, and especially affects people with chronic obstructive pulmonary disease. Selected surface antigens of this organism will be evaluated for their vaccinogenic potential. An animal model system will be utilized to measure the effects of active immunization regimens on pulmonary clearance rates. Recombinant DNA techniques will be used to clone the genes encoding the P2 major outer membrane protein and the P6 lipoproteins of NTHI. The resultant recombinant proteins will be purified from E. coli in a form free from contamination with other NTHI antigens. These purified proteins will be studied for their ability to induce pulmonary immunity to NTHI. A previously undescribed surface antigen of NTHI, which has been shown to be a target for monoclonal antibodies which enhance pulmonary clearance of NTHI, will also be purified and evaluated for its vaccinogenic potential. Finally, monoclonal antibody technology will be used in conjunction with the animal model system to investigate the role of antibody isotype in immune defense in the lung.